engleski

TPMT Gene Polymorphisms in Croatian Population

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of azathioprine (AZA), 6-mercaptopurine (6-MP) and thioguanine, medications widely used to treat malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel disease and solid organ transplantat rejection. Low TPMT activity plays a significant role in the occurence of life-threatening myelosupression, a serious toxicity of thiopurine drugs. Altered TPMT activity predominantly results from single nucleotide polymorphisms (SNPs). To date, eight TPMT alleles have been identified, including three alleles (TPMT*2, TPMT*3A and TPMT*3C) which account for 80-95% of intermediate or low enzyme activity. Ten percent of individuals with intermediate activity are heterozygous at the TPMT gene locus and 0.3% are homozygous for low activity alleles. The aim of our study was to estimate allelic frequency for three SNPs in TPMT gene in the Croatian population. DNAs obtained from 350 unrelated individuals were genotyped for the TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C SNPs using allele-specific PCR or PCR-RFLP method. The frequency of heterozygous TPMT genotype in Croatian population was 5.7%. The frequency of the three allelic variants of the TPMT gene were: 0.6% for TPMT*2, 4.2% for TPMT*3A, and 0.9% for TPMT*3C. The TPMT*3B allele was not detected in any of the samples analyzed. In conclusion, this study demonstrate that the TPMT*3A allele is a common allele in the Croatian population. The low frequency of heterozygous TPMT genotype in Croatian population can be explained by interethnic variations of TPMT alleles. In our oppinion this information would be helpful for identifying patients at high risk of inadequate responses to thiopurine therapy.

TPMT; polymorphisms; pharmacogenetics

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